Verbascoside and isoverbascoside ameliorate transforming growth factor ß1-induced collagen expression by lung fibroblasts through Smad/non-Smad signaling pathways.

AIMS: Pulmonary fibrosis (PF) is a chronic, irreversible, and debilitating lung disease that typically leads to respiratory failure, and is a major cause of morbidity and mortality. Few drugs are effective for the treatment of patients with PF or for reducing the rate of disease progression. MAIN METHODS: Transforming growth factor-ß1 (TGF-ß1) is a profibrotic cytokine that signals through Smad and non-Smad pathways. Verbascoside (VB) and isoverbascoside (isoVB) exhibit anti-oxidative and anti-inflammatory activities, however, their anti-fibrotic effects remain unclear. This study evaluated the effects of VB and isoVB on TGF-ß1-stimulated murine lung fibroblasts (MLg 2908) and also human lung fibroblasts (confirmed by immunostaining). KEY FINDINGS: Neither VB nor isoVB had a cytotoxic effect on MLg 2908 fibroblasts. Both compounds (10 µM) reduced intracellular reactive oxygen species and markedly attenuated collagen I expression in TGF-ß1 (5 ng/ml)-induced MLg 2908 cells compared to TGF-ß1 alone. Both compounds suppressed the TGF-ß1-induced phosphorylation of Smad2/3 and ERK/p38 mitogen-activated protein kinases (MAPKs). VB and isoVB, but not pirfenidone and nintedanib, inhibited TGF-ß1-induced pSmad2/3, ERK/p38 MAPK, and collagen I expression. VB and isoVB also decreased collagen I deposition in TGF-ß1-induced MLg 2908 cells. Only isoVB significantly suppressed collagen I deposition in TGF-ß1-induced human pulmonary cells. Our results indicated that VB and isoVB may exert antifibrotic effects by inhibiting TGF-ß1-induced collagen I expression via inhibition of oxidative stress and downregulation of the Smad/non-Smad pathway. SIGNIFICANCE: The present findings suggest that VB or isoVB may be used as a supplement to alleviate PF.

AST-120 Improves Cardiac Dysfunction in Acute Kidney Injury Mice via Suppression of Apoptosis and Proinflammatory NF-κB/ICAM-1 Signaling.

PURPOSE: Acute kidney injury (AKI) is a devastating disorder associated with considerably high morbidity and mortality. Reports have shown that AST-120, an oral charcoal adsorbent, can reduce oxidative stress by lowering serum indoxyl sulfate levels. The effects of AST-120 and indoxyl sulfate on kidney injury and cardiac dysfunction were investigated in vivo and in vitro. PATIENTS AND METHODS: Patients were tracked for enrollment upon receiving a diagnosis of AKI. Plasma was collected to determine the renal and inflammatory parameters. Renal ischemia/reperfusion (I/R) induced AKI or sham operation was performed in C57BL/6J mice. Animals were divided into sham, AKI+vehicle, and AKI+AST-120 groups. Plasma and tissues were assembled after 48 h to assess apoptotic and inflammatory responses. We also conducted human umbilical vein endothelial cell (HUVECs) and HL-1 cardiomyocyte culture studies to determine the underlying mechanisms of indoxyl sulfate's effects. Echocardiography, histopathology, biochemical indexes, ELISA, terminal dUTP nick-end labeling (TUNEL) and Western blot analysis were performed. RESULTS: The cohort included 25 consecutive patients with AKI and 25 non-AKI. Plasma levels of creatinine, indoxyl sulfate, IL-1ß and ICAM-1 were significantly higher in patients with AKI than in non-AKI controls. Plasma levels of blood urea nitrogen, creatinine, indoxyl sulfate, IL-1ß and renal tubular injury were increased in mice after renal I/R and were decreased by AST-120 treatment. In addition, AST-120 therapy not only improved the parameters assessed by echocardiography but also substantially attenuated the elevation of plasma BNP. Oral administration of AST-120 significantly downregulated NF-κB/ICAM-1 expression and reduced cell apoptosis in both kidney and heart after renal I/R injury. CONCLUSION: Our investigations demonstrated that AST-120 administration improves cardiac dysfunction in AKI mice via the suppression of apoptosis and proinflammatory NF-κB/ICAM-1 signaling.

Antcamphin M Inhibits TLR4-Mediated Inflammatory Responses by Upregulating the Nrf2/HO-1 Pathway and Suppressing the NLRP3 Inflammasome Pathway in Macrophages.

The medicinal mushroom Antrodia cinnamomea has been demonstrated to have anti-inflammatory properties. However, the bioactive compounds in A. cinnamomea need further investigation. The present study aimed to understand the mechanism of action of antcamphin M, an ergostanoid isolated from A. cinnamomea mycelium and to clarify its underlying mechanisms of action. RAW264.7 cells were pretreated with the indicated concentrations of antcamphin M, prior to stimulation with lipopolysaccharide (LPS). Cell viability, production of nitric oxide (NO), prostaglandin E2 (PGE2), cytokines, and chemokines, as well as the inflammation-related signaling pathways were investigated. The study revealed that antcamphin M significantly decreased the LPS-induced production of NO, PGE2, pro-inflammatory cytokines, and keratinocyte chemoattractant CXCL1 (KC), along with the levels of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins without significant cytotoxicity, indicating it had a better anti-inflammatory activity than that of gisenoside Rb1 and Rg1. Additionally, antcamphin M significantly inhibited the activation of MAPKs (p38, ERK, and JNK), NFκB, and components of the NLRP3 inflammasome (NLRP3, ASC, and caspase-1) signaling pathways and also increased the levels of nuclear factor erythroid-2-related factor (Nrf2) and heme oxygenase-1 (HO-1). These findings suggest that antcamphin M possesses potent anti-inflammatory activities and could be a potential candidate for the development of anti-inflammatory drugs.

Advanced Molecular Knowledge of Therapeutic Drugs and Natural Products Focusing on Inflammatory Cytokines in Asthma.

Asthma is a common respiratory disease worldwide. Cytokines play a crucial role in the immune system and the inflammatory response to asthma. Abnormal cytokine expression may lead to the development of asthma, which may contribute to pathologies of this disease. As cytokines exhibit pleiotropy and redundancy characteristics, we summarized them according to their biologic activity in asthma development. We classified cytokines in three stages as follows: Group 1 cytokines for the epithelial environment stage, Group 2 cytokines for the Th2 polarization stage, and Group 3 cytokines for the tissue damage stage. The recent cytokine-targeting therapy for clinical use (anti-cytokine antibody/anti-cytokine receptor antibody) and traditional medicinal herbs (pure compounds, single herb, or natural formula) have been discussed in this review. Studies of the Group 2 anti-cytokine/anti-cytokine receptor therapies are more prominent than the studies of the other two groups. Anti-cytokine antibodies/anti-cytokine receptor antibodies for clinical use can be applied for patients who did not respond to standard treatments. For traditional medicinal herbs, anti-asthmatic bioactive compounds derived from medicinal herbs can be divided into five classes: alkaloids, flavonoids, glycosides, polyphenols, and terpenoids. However, the exact pathways targeted by these natural compounds need to be clarified. Using relevant knowledge to develop more comprehensive strategies may provide appropriate treatment for patients with asthma in the future.

Sweet Olive Extract Attenuates Dextran Sulfate Sodium-Induced Colitis in Mice.

Sweet olive (Osmanthus fragrans flowers) is used to treat dysentery and reduce phlegm and stasis in traditional Chinese medicine. Recently, we found that verbascoside, the major component in the sweet olive ethanolic extract (OFE), inhibited IL-8 secretion in human colorectal adenocarcinoma WiDr cells. However, evidence-based treatment of inflammatory bowel disease (IBD) with the extract is yet to be performed. To evaluate the therapeutic effect of OFE, we measured IL-8 suppression by OFE and verbascoside in a WiDr cell culture assay. In the IL-8 secretion assay, both OFE (100 µg/mL) and verbascoside (10 µM) significantly inhibited IL-8 production in WiDr cells. Furthermore, we designed cotreated (dextran sulfate sodium [DSS]+OFE-treated) and post-treated (DSS-OFE-treated) protocols to access the therapeutic effects of OFE in vivo. Mice treated with 500 mg/kg per day OFE exhibited significant improvement in IBD symptoms, including disease activity index score, body weight, and colon length maintenance. The suppressive effects on myeloperoxidase expression and lower histopathology scores (including neutrophil infiltration) for the colon were also found. These findings suggest that OFE exerts anti-inflammatory effect on DSS-induced colitis.

Antrolone, a Novel Benzoid Derived from Antrodia cinnamomea, Inhibits the LPS-Induced Inflammatory Response in RAW264.7 Macrophage Cells by Balancing the NF-[Formula: see text]B and Nrf2 Pathways.

Antrodia cinnamomea, a medicinal mushroom, has previously demonstrated anti-inflammatory activity, although the specific compound responsible for the effect remains unclear. The present study was designed to investigate the anti-inflammatory property of antrolone, a novel benzoid derived from A. cinnamomea mycelium, and to clarify the underlying mechanisms of action. To this end, murine macrophage RAW264.7 cells were treated with antrolone (0.1-30[Formula: see text][Formula: see text]M) 30[Formula: see text]min prior to stimulation with lipopolysaccharides (LPS, 0.1[Formula: see text][Formula: see text]g/ml) for 24[Formula: see text]h. Cell viability, nitric oxide (NO) and prostaglandin E2 (PGE2) production, levels of pro-inflammatory cytokines and chemokines, and the signaling pathways involved in the inflammatory cascades were then investigated. Our results show that antrolone significantly decreased LPS-induced NO, PGE2, pro-inflammatory cytokine, and keratinocyte chemoattractant CXCL1 (KC) production and reduced levels of the proteins inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2). These effects were independent of the effect of antrolone on macrophage cytotoxicity. Moreover, antrolone significantly inhibited the activation of the NF[Formula: see text]B, MAPK, and AKT pathways, while it increased nuclear factor erythroid-2-related factor (Nrf2) and heme oxygenase-1 (HO-1) levels. Our findings suggest that antrolone exhibits potent anti-inflammatory activity and may, therefore, be a lead compound for the development of an anti-inflammatory drug.

Suppression of IL-8 Release by Sweet Olive Ethanolic Extract and Compounds in WiDr Colon Adenocarcinoma Cells.

Oxidative stress can stimulate the secretion of pro-inflammatory cytokines. Interleukin-8 (IL-8) has been implicated in the pathogenesis of inflammatory bowel disease and the metastatic spread of colorectal cancer. The flowers of Osmanthus fragrans (sweet olive) are used to alleviate dysentery with blood in the bowel, as well as stomach ache and diarrhea. However, the evidence of their therapeutic effects on these symptoms remains unclear. In the present study, the protective effects of sweet olive flower ethanolic extract (OFE) against oxidative stress in WiDr cells was assessed by evaluating its 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity. In addition, cellular IL-8 secretion was evaluated. Notably, high-performance liquid chromatography showed verbascoside to be the primary constituent in OFE; it exhibited a DPPH scavenging activity with an IC50 of 8.23 µg/mL. Moreover, OFE (1 to 100 µg/mL) showed a potent, dose-dependent inhibitory effect on H2 O2 -induced IL-8 secretion in WiDr cells. Nine compounds were isolated from OFE based on a protective effect-guided purification process. Of these compounds, 5 phenolic compounds-verbascoside, phillygenin, tyrosol, methyl 4-hydroxycinnamate, and eutigoside A-reduced IL-8 secretion at 10 µg/mL treatment concentrations. Further analysis showed that the anti-inflammatory effects of OFE likely occurred via nuclear factor-κB pathway inhibition, which attenuates IL-8 secretion in cells. Collectively, these data suggest that OFE could be developed as an agent that suppresses IL-8 secretion to treat chronic inflammatory diseases.

Rhodiola crenulata extract counteracts the effect of hypobaric hypoxia in rat heart via redirection of the nitric oxide and arginase 1 pathway.

BACKGROUND: Rhodiola crenulata is traditionally used as a folk medicine in Tibet for preventing high-altitude illnesses, including sudden cardiac death (SCD). The cardio-protective effects of Rhodiola crenulata root extract (RCE) against hypoxia in vivo have been recently confirmed. However, the way in which RCE produces these effects remains unclear. The present study is designed to confirm the protective effects of RCE on the heart in acute hypobaric hypoxia exposure and examine the mechanisms by which this occurs. METHODS: Sprague-Dawley (SD) rats were pretreated with or without RCE and then exposed to a simulated altitude of 8000 m in a hypobaric hypoxia chamber for 9 h. The expression of cardiac arginase 1 (Arg-1) and endothelial nitric oxide synthase (eNOS) and the activity of associated signaling pathways was examined. RESULTS: Hypoxia reduced cardiac eNOS phosphorylation and increased Arg-1 expression, but both responses were reversed by RCE pre-treatment. In addition, RCE decreased the hypoxia-induced oxidative stress markers of reactive oxygen species (ROS) production, malondialdehyde (MDA) level, and protein carbonyl content. Furthermore, RCE protected cardiomyocytes from hypoxia-induced cardiac apoptosis and restored the phosphorylation level of AKT and p38 MAPK as well as the superoxide dismutase 2 (SOD2) content in hypoxic animals. CONCLUSION: The findings provide evidence that the effects of Rhodiola crenulata against altitude illness are partially mediated by modulation of eNOS and Arg-1 pathways in the heart.

Rhodiola crenulata extract regulates hepatic glycogen and lipid metabolism via activation of the AMPK pathway.

BACKGROUND: Metabolic syndrome may lead to many complications, such as nonalcoholic fatty liver disease (NAFLD). A natural and effective therapeutic agent for patients with NAFLD is urgently needed. In a previous study, we showed that Rhodiola crenulata root extract (RCE) regulated hepatic gluconeogenesis through activation of AMPK signaling. However, the manner in which RCE regulates hepatic lipid and glycogen metabolism remains unclear. The current study was conducted to investigate the effects of RCE on hepatic glycogen and lipid metabolism, as well as the mechanisms underlying such effects. METHODS: Human hepatoma HepG2 cells were treated with RCE for 6 h under high glucose conditions, after which glycogen synthesis, lipogenesis, and relative gene expression were examined. In addition, lipogenesis-related genes were investigated in vivo. RESULTS: RCE significantly increased glycogen synthesis and inhibited lipogenesis, while regulating genes related to these processes, including glycogen synthase kinase 3ß (GSK3ß), glycogen synthase (GS), fatty acid synthase (FAS), CCAAT/enhancer-binding protein (C/EBP), and sterol regulatory element-binding protein 1c (SREBP-1c). However, the effects caused by RCE were neutralized by compound C, an AMPK antagonist. Further studies showed that expression levels of lipogenic genes decreased at the protein and mRNA levels in the rat liver. CONCLUSIONS: Our results demonstrate that RCE regulates hepatic glycogen and lipid metabolism through the AMPK signaling pathway. These results suggest that RCE is a potential intervention for patients with NAFLD.

Rhodiola crenulata extract suppresses hepatic gluconeogenesis via activation of the AMPK pathway.

BACKGROUND: Rhodiola, a popular herb, has been used for treating high altitude sicknesses, depression, fatigue, and diabetes. However, the detailed mechanisms by which Rhodiola crenulata functions in the liver need further clarification. PURPOSE: The current study was designed to examine the effects of Rhodiola crenulata root extract (RCE) on hepatic glucose production. METHODS: Human hepatoma HepG2 cells were treated with RCE for 6 h. Glucose production, the expression level of p-AMPK, and the expression of key gluconeogenic genes were measured. The effects of RCE were also studied in Sprague-Dawley (SD) rats. The efficacy and underlying mechanism of RCE in the liver were examined. RESULTS: RCE significantly suppressed glucose production and gluconeogenic gene expression in HepG2 cells while activating the AMPK signaling pathway. Interestingly, RCE-suppressed hepatic gluconeogenesis was eliminated by an AMPK-specific inhibitor, but not by the PI3K/AKT-specific inhibitor. In addition, oral administration of RCE significantly increased phosphorylated AMPK levels and inhibited gluconeogenic gene expression in the rat liver. Furthermore, RCE treatment also decreased plasma glucose concentration in rats. CONCLUSION: We present in vitro and in vivo evidence that RCE might exert the glucose-lowering effect partly by inhibiting hepatic gluconeogenesis through activating the AMPK signaling pathway. These findings provide evidence that Rhodiola crenulata may be helpful for the management of type II diabetes.

Cytotoxic effect of triterpenoids from the root bark of Hibiscus syriacus.

In this study, 4 new triterpenoids-3ß- acetoxy-olean-11-en,28,13ß-olide (1), 3ß- acetoxy-11α,12α-epoxy-olean-28,13ß-olide (2), 19α-epi-betulin (3), and 20, 28-epoxy-17ß,19ß-lupan-3ß-ol (4)-and 12 known compounds, were isolated from the root bark of Hibiscus syriacus L. by using acetone extraction. Their structures were characterized by extensive spectroscopic analysis. To investigate cytotoxicity, A549 human lung cancer cells were exposed to the extract and the compounds identified from it. Significantly reduced cell viability was observed with betulin-3-caffeate (12) (IC50, 4.3 µM). The results of this study indicate that betulin-3-caffeate (12) identified from H. syriacus L. may warrant further investigation for potential as anticancer therapies.

Cytotoxic cardiac glycosides and coumarins from Antiaris toxicaria.

Eight new cardiac glycosides/aglycones (antiaritoxiosides A-G, 1-7, and antiarotoxinin B, 8), two new coumarins (anticarins A-B, 41-42), and two new flavanones (antiarones L-K, 43-44) were isolated from trunk bark of Antiaris toxicaria together with 53 known compounds. The new structures were established by extensive analysis of spectroscopic data. Compound 1 (10-carboxy and 3α-hydroxy) and compounds 3-6 (10-hydroxy) contain unique substituents that are rarely found in cardiac glycosides. The cytotoxic effects of isolated compounds against ten human cancer cell lines, KB, KB-VIN, A549, MCF-7, U-87-MG, PC-3, 1A9, CAKI-1, HCT-9 and S-KMEL-2, were tested using the sulforhodamine B assay. Five compounds (12, 16, 20, 22, and 31) showed significant cytotoxicity against all ten cancer cell lines, with notable potency at the ng/mL level against some cell lines, which merits further development as clinical trial candidates.

Alkaloids from Coptis chinensis root promote glucose uptake in C2C12 myotubes.

The root of Coptis chinensis Franch. (COCH) is regularly used for medicinal purposes, and has been prescribed alone or in combination with other traditional herbs for the treatment of diabetes. To investigate the effects of COCH on glucose utilization by skeletal muscles, we prepared an ethanol extract of COCH root (COCH-Et) partitioned with dichloromethane, n-butanol, and water and tested its effects on glucose uptake in differentiated C2C12 myotubes. We found that dichloromethane and n-butanol sub-fractions of COCH-Et promoted glucose uptake in differentiated C2C12 cells at 50 µg/mL. Further fractionation of these preparations by using column chromatography, analysis of their effects on glucose uptake and characterization using nuclear magnetic resonance, mass spectrometry, and thin layer chromatography helped identify two new alkaloids, 8,13-dioxocoptisine hydroxide (1) and coptisonine (2), together with eleven known compounds. These were isolated from the dichloromethane layer of COCH-Et. In particular, exposure of C2C12 cells to berberine (6) at 12.5 and 6.25 µg/mL for 24h resulted in significant promotion of glucose uptake. Coptisonine (2) and octadecyl caffeate (9) also stimulated glucose uptake at 25 and 50 µg/mL. These findings indicate that active constituents of COCH root may help alleviate hyperglycemia in diabetes by promoting glucose uptake by skeletal muscles.

Rhodiola crenulata and Its Bioactive Components, Salidroside and Tyrosol, Reverse the Hypoxia-Induced Reduction of Plasma-Membrane-Associated Na,K-ATPase Expression via Inhibition of ROS-AMPK-PKC ξ Pathway.

Exposure to hypoxia leads to impaired pulmonary sodium transport, which is associated with Na,K-ATPase dysfunction in the alveolar epithelium. The present study is designed to examine the effect and mechanism of Rhodiola crenulata extract (RCE) and its bioactive components on hypoxia-mediated Na,K-ATPase endocytosis. A549 cells were exposed to hypoxia in the presence or absence of RCE, salidroside, or tyrosol. The generation of intracellular ROS was measured by using the fluorescent probe DCFH-DA, and the endocytosis was determined by measuring the expression level of Na,K-ATPase in the PM fraction. Rats exposed to a hypobaric hypoxia chamber were used to investigate the efficacy and underlying mechanism of RCE in vivo. Our results showed that RCE and its bioactive compounds significantly prevented the hypoxia-mediated endocytosis of Na,K-ATPase via the inhibition of the ROS-AMPK-PKC ζ pathway in A549 cells. Furthermore, RCE also showed a comparable preventive effect on the reduction of Na,K-ATPase endocytosis and inhibition of AMPK-PKC ξ pathway in the rodent model. Our study is the first to offer substantial evidence to support the efficacy of Rhodiola products against hypoxia-associated Na,K-ATPase endocytosis and clarify the ethnopharmacological relevance of Rhodiola crenulata as a popular folk medicine for high-altitude illness.

Rhodiola crenulata Extract Alleviates Hypoxic Pulmonary Edema in Rats.

Sudden exposure of nonacclimatized individuals to high altitude can easily lead to high altitude illnesses. High altitude pulmonary edema (HAPE) is the most lethal form of high altitude illness. The present study was designed to investigate the ability of Rhodiola crenulata extract (RCE), an herbal medicine traditionally used as an antiacute mountain sickness remedy, to attenuate hypoxia-induced pulmonary injury. Exposure of animals to hypobaric hypoxia led to a significant increase in pathological indicators for pulmonary edema, including the lung water content, disruption of the alveolar-capillary barrier, and protein-rich fluid in the lungs. In addition, hypobaric hypoxia also increased oxidative stress markers, including (ROS) production, (MDA) level, and (MPO) activity. Furthermore, overexpression of plasma (ET-1), (VEGF) in (BALF), and (HIF-1 α ) in lung tissue was also found. However, pretreatment with RCE relieved the HAPE findings by curtailing all of the hypoxia-induced lung injury parameters. These findings suggest that RCE confers effective protection for maintaining the integrity of the alveolar-capillary barrier by alleviating the elevated ET-1 and VEGF levels; it does so by reducing hypoxia-induced oxidative stress. Our results offer substantial evidence to support arguments in favor of traditional applications of Rhodiola crenulata for antihigh altitude illness.

The Ethanol Extract of Osmanthus fragrans Flowers Reduces Oxidative Stress and Allergic Airway Inflammation in an Animal Model.

The Osmanthus fragrans flower, a popular herb in Eastern countries, contains several antioxidant compounds. Ben Cao Gang Mu, traditional Chinese medical literature, describes the usefulness of these flowers for phlegm and stasis reduction, arrest of dysentery with blood in the bowel, and stomachache and diarrhea treatment. However, modern evidence regarding the therapeutic efficacy of these flowers is limited. This study was aimed at assessing the antioxidative effects of the ethanol extract of O. fragrans flowers (OFE) in vivo and evaluating its antioxidant maintenance and therapeutic effect on an allergic airway inflammation in mice. After OFE's oral administration to mice, the values obtained in the oxygen radical absorbance capacity assay as well as the glutathione concentration in the lungs and spleens of mice increased while thiobarbituric acid reactive substances decreased significantly, indicating OFE's significant in vivo antioxidant activity. OFE was also therapeutically efficacious in a mouse model of ovalbumin-induced allergic airway inflammation. Orally administered OFE suppressed ovalbumin-specific IgE production and inflammatory cell infiltration in the lung. Moreover, the antioxidative state of the mice improved. Thus, our findings confirm the ability of the O. fragrans flowers to reduce phlegm and suggest that OFE may be useful as an antiallergic agent.

Biologically active constituents from the fruiting body of Taiwanofungus camphoratus.

Five new benzenoids, benzocamphorins A-E (1-5), and 10 recently isolated triterpenoids, camphoratins A-J (16-25), together with 23 known compounds including seven benzenoids (6-12), three lignans (13-15), and 13 triterpenoids (26-38) were isolated from the fruiting body of Taiwanofungus camphoratus. Their structures were established by spectroscopic analysis. Selected compounds were examined for cytotoxic and anti-inflammatory activities. Compounds 9 and 21 showed moderate cytotoxicity against MCF-7 and Hep2 cell lines with ED(50) values of 3.4 and 3.0µg/mL, respectively. Compounds 21, 25, 26, 29-31, 33, and 36 demonstrated potent anti-inflammatory activity by inhibiting lipopolysaccharide (LPS)-induced nitric oxide (NO) production with IC(50) values of 2.5, 1.6, 3.6, 0.6, 4.1, 4.2, 2.5, and 1.5µM, respectively, which were better than those of the nonspecific nitric oxide synthase (NOS) inhibitor N-nitro-l-arginine methyl ester (l-NAME) (IC(50): 25.8µM). These results may substantiate the use of T. camphoratus in traditional Chinese medicine (TCM) for the treatment of inflammation and cancer-related diseases. The newly discovered compounds deserve further development as anti-inflammatory candidates.

Cardiac glycosides from Antiaris toxicaria with potent cardiotonic activity.

An ethanolic extract of Antiaris toxicaria trunk bark showed potent in vitro cardiotonic effect on isolated guinea pig atria. Bioassay-guided fractionation of the extract led to identification of nine new cardiac glycosides (1-9, named antiarosides A-I), antiarotoxinin A (10), and 18 known compounds. Their structures were established using MS and NMR spectroscopic studies, including homonuclear and heteronuclear correlation experiments. The ability of these cardiotonic compounds to produce positive inotropic action and their safety indexes were examined in comparison with those of ouabain, a classical inhibitor of Na(+)/K(+)-ATPase. Malayoside (23) was nearly equipotent and had a similar safety index to ouabain in guinea pig atria. However, the maximal positive inotropic effect and safety index of 23 in papillary muscle were better than those of ouabain. An electrophysiological recording showed that 23 inhibited the sodium pump current in a concentration-dependent manner.

Cytotoxic phenanthroindolizidine alkaloids from the roots of Ficus septica.

Activity-monitored fractionation of the CHCl3 solubles of the MeOH extract of the roots of Ficus septica using cytotoxicity assay led to the isolation of twenty phenanthroindolizidine alkaloids, including ten new ficuseptines E-N and ten known compounds. The cytotoxic effects of some of the isolates were tested on gastric adenocarcinoma (NUGC) and nasopharyngeal carcinoma (HONE-1) cell lines and the results demonstrated that, with the exception of dehydrotylophorine, all the tested compounds displayed pronounced cytotoxic activity with significant cell growth inhibitory effects. In addition, 13a R-antofine was found to be highly effective with ED(50) values of < 0.1 microg/mL against L-1210, P-388, A-549 and HCT-8 cell lines in another assay.

Antioxidant properties of royal jelly associated with larval age and time of harvest.

This study aimed to evaluate the antioxidant properties of royal jelly (RJ) collected from larvae of different ages that were transferred in artificial bee queen cells for 24, 48, and 72 h. RJ harvested from the 1 day old larvae 24 h after the graft displayed predominant antioxidant properties, including scavenging activity of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals, inhibition of linoleic acid peroxidation, and reducing power. Regardless of the initial larval age, lower antioxidant activities were observed in the RJ harvested later than 24 h except for the activity of superoxide dismutase. In addition, higher contents of proteins and polyphenolic compounds were determined in the RJ harvested 24 h than that harvested 48 or 72 h after the graft. It implied that the polyphenolic compounds may be the major component for giving the antioxidant activities in RJ. In summary, the time of harvest and the initial larval age did affect the antioxidant potencies in RJ, and RJ collected 24 h after the larval transfer showed the most substantial antioxidant activities.